6-41957421-G-A

Position:

• chr6-41957421-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000372988.8(CCND3):​c.-45-16836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,138 control chromosomes in the GnomAD database, including 2,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2977 hom., cov: 32)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.680

Genes affected

CCND3 (HGNC:1585): (cyclin D3) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 6-41957421-G-A is Benign according to our data. Variant chr6-41957421-G-A is described in ClinVar as [Benign]. Clinvar id is 1282713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-45-16836C>T		intron_variant			NP_001129489.1
CCND3	NM_001136126.3	c.-174-20027C>T		intron_variant			NP_001129598.1
CCND3	NM_001287434.2	c.-174-20027C>T		intron_variant			NP_001274363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372988.8	c.-45-16836C>T		intron_variant		1		ENSP00000362079
CCND3	ENST00000415497.6	c.-174-20027C>T		intron_variant		2		ENSP00000401595
CCND3	ENST00000502771.1	c.-45-16836C>T		intron_variant		4		ENSP00000425334

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26886 AN: 152020 Hom.: 2974 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.177 AC: 26891 AN: 152138 Hom.: 2977 Cov.: 32 AF XY: 0.177 AC XY: 13142 AN XY: 74368

Gnomad4 AFR AF: 0.0508

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.168

Alfa AF: 0.229 Hom.: 5290

Bravo AF: 0.166

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 23, 2021

This variant is associated with the following publications: (PMID: 22929040) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.7
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9349205; hg19: chr6-41925159;